BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no ... [more ▼]

BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no spontaneously breathing efforts. This research presents a time-varying elastance (Edrs) model that can be used in spontaneously breathing patients to determine their respiratory mechanics. METHODS: A time-varying respiratory elastance model is developed with a negative elastic component (Edemand), to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS) and Neurally Adjusted Ventilatory Assist (NAVA) are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. Edrs of every breathing cycle for each patient at different ventilation modes are presented for comparison. RESULTS: At the start of every breathing cycle initiated by patient, Edrs is < 0. This negativity is attributed from the Edemand due to a positive lung volume intake at through negative pressure in the lung compartment. The mapping of Edrs trajectories was able to give unique information to patients' breathing variability under different ventilation modes. The area under the curve of Edrs (AUCEdrs) for most patients is > 25 cmH2Os/l and thus can be used as an acute respiratory distress syndrome (ARDS) severity indicator. CONCLUSION: The Edrs model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes. [less ▲]

OBJECTIVES: Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). STUDY DESIGN: In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34kg/m(2)), a COC containing 30mcg ethinylestradiol (EE) and 3mg drospirenone (DRSP) was used for 3cycles, followed by 6cycles of the same COC combined with either 50mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Delta4-androstenedione (AD), 3alpha-androstanediol glucuronide (ADG) and estradiol (E2) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo). RESULTS: During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period - 1.3+/-1.2nmol/L vs. 0.0+/-0.4nmol/L; p<.0001) - and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E2. CONCLUSIONS: An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG. IMPLICATIONS: When using a COC that increases SHBG considerably, a daily dose of 50mg DHEA is insufficient to normalize free T levels completely. [less ▲]

The number of image analysis tools supporting the extraction of architectural features of root systems has increased over the last years. These tools offer a handy set of complementary facilities, yet it ... [more ▼]

The number of image analysis tools supporting the extraction of architectural features of root systems has increased over the last years. These tools offer a handy set of complementary facilities, yet it is widely accepted that none of these software tool is able to extract in an efficient way growing array of static and dynamic features for different types of images and species. . We describe the Root System Markup Language (RSML) that has been designed to overcome two major challenges: (i) to enable portability of root architecture data between different software tools in an easy and interoperable manner allowing seamless collaborative work, and (ii) to provide a standard format upon which to base central repositories which will soon arise following the expanding worldwide root phenotyping effort. RSML follows the XML standard to store 2D or 3D image metadata, plant and root properties and geometries, continuous functions along individual root paths and a suite of annotations at the image, plant or root scales, at one or several time points. Plant ontologies are used to describe botanical entities that are relevant at the scale of root system architecture. An xml-schema describes the features and constraints of RSML and open-source packages have been developed in several languages (R, Excel, Java, Python, C#) to enable researchers to integrate RSML files into popular research workflow. [less ▲]

This paper aims at presenting a general versatile time integration scheme applicable to anisotropic damage coupled to elastoplasticity, considering any damage rate and isotropic hardening formulations ... [more ▼]

This paper aims at presenting a general versatile time integration scheme applicable to anisotropic damage coupled to elastoplasticity, considering any damage rate and isotropic hardening formulations. For this purpose a staggered time integration scheme in a finite strain framework is presented, together with an analytical consistent tangent operator. The only restrictive hypothesis is to work with an undamaged isotropic material, assumed here to follow a J2 plasticity model. The only anisotropy considered is thus a damage-induced anisotropy. The possibility to couple any damage rate law with the present algorithm is illustrated with a classical ductile damage model for aluminium, and a biological damage-like application. The later proposes an original bone remodelling law coupled to trabecular bone plasticity for the simulation of orthodontic tooth movements. All the developments have been considered in the framework of the implicit non-linear finite element code Metafor (developed at the LTAS/MN2L, University of Liège, Belgium - www.metafor.ltas.ulg.ac.be). [less ▲]

In this article, the ability of the 2D shallow water equations to model meandering flows in shallow rectangular reservoirs is discussed. Four meandering flows, of various shallowness, were modelled using ... [more ▼]

In this article, the ability of the 2D shallow water equations to model meandering flows in shallow rectangular reservoirs is discussed. Four meandering flows, of various shallowness, were modelled using the academic flow model WOLF 2D, which includes a depth-averaged k- model accounting for the horizontal and vertical turbulent length-scales. The bottom friction was modelled with the Colebrook-White formula and different roughness heights were considered. A Proper Orthogonal Decomposition (POD) was applied to the simulation results to extract the behaviour of the main structures responsible for the meandering flow. The same POD analysis was also performed for the reference experimental flow fields, obtained by Large-Scale Particle Image Velocimetry. The first two POD modes obtained from the numerical simulations assuming a smooth bottom are in good agreement with the experimental modes in terms of energy, as well as temporal and spatial variations, whatever the shallowness. In contrast, the remaining simulated modes are not well rendered. The effect of an increased roughness height in the simulations is finally discussed. It leads to an improved reproduction of the first two modes and of the following modes, except when significant viscous effects govern in the flow. [less ▲]

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries ... [more ▼]

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Both effects were very consistent across the trials and they represent some advantages for SGLT2 inhibitors when compared with other oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, and prescribing information for each SGLT2 inhibitor should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Caution is also recommended in the elderly population because of a higher risk of renal impairment, orthostatic hypotension and dehydration, even if the absence of hypoglycaemia represents an obvious advantage in this population. The overall effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and will be evaluated in several ongoing prospective placebo-controlled trials with cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy also deserve more attention. SGLT2 inhibitors are generally well-tolerated. The most frequently reported adverse events are female genital mycotic infections, while urinary tract infections are less commonly observed and generally benign. In conclusion, with their unique mechanism of action that is independent of insulin secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic options available for the management of T2DM at any stage in the natural history of the disease. Although SGLT2 inhibitors have already been extensively investigated, further studies should even better delineate the best place of these new glucose-lowering agents in the already rich armamentarium for the management of T2DM. [less ▲]

Poly(ethylene oxide) (PEO)-b-polyphosphate copolymers made of hydrophilic PEO and hydrophobic polyphosphates are amphiphilic copolymers prone to self-assemble in water into nanoparticles. In this work ... [more ▼]

Poly(ethylene oxide) (PEO)-b-polyphosphate copolymers made of hydrophilic PEO and hydrophobic polyphosphates are amphiphilic copolymers prone to self-assemble in water into nanoparticles. In this work, nanoparticles are obtained by the self-assembly of PEO-b-polyphosphate copolymers in water in the absence of any organic co-solvent whatever the length of the pendant alkyl chain (between 4 and 7 carbon atoms) of the polyphosphate block. Remarkably, this solvent-free process remains efficient even for the most hydrophobic polyphosphate blocks. The critical aggregation concentration (CAC) of the block copolymers was determined by pyrene probe fluorescence. Finally, the efficiency of these copolymer surfactants to decrease the air–water interface was measured by air-bubble tensiometry. [less ▲]

The River Elbe is responsible for influxes of contaminants into the Wadden Sea World Heritage Site. We investigated levels of polychlorinated biphenyls (PCBs), oxychlordane (OxC), hexachlorobenzene (HCB ... [more ▼]

The River Elbe is responsible for influxes of contaminants into the Wadden Sea World Heritage Site. We investigated levels of polychlorinated biphenyls (PCBs), oxychlordane (OxC), hexachlorobenzene (HCB), hexachlorocyclohexanes (α-, β-, γ-HCHs), dichlorodiphenyltrichloroethane (DDT) and its metabolites, and polybrominated diphenyl ethers (PBDEs) in blood and feathers from Eurasian oystercatchers (Haematopus ostralegus; n=28) at the Elbe and compared it with a non-riverine site about 90 km further north. (1) Mean levels of all contaminants in feathers and serum were significantly higher at the river (ƩPCBs: 27.6 ng/g feather, 37.0 ng/ml serum; ƩDDTs: 5.3 ng/g feather, 4.4 ng/ml serum) compared with the non-riverine site (ƩPCBs: 6.5 ng/g feather, 1.2 ng/ml serum; ƩDDTs: 1.4 ng/g feather, 0.5 ng/ml serum). Mean ƩHCH and HCB levels were <1.8 ng/g in feather and <1.8 ng/ml in serum at both sites. (2) Levels of most detectable compounds in serum and feathers were significantly related, but levels were not consistently higher in either tissue. (3) There was no significant relationship between trophic level in individual oystercatchers (expressed as δ15N) or the degree of terrestrial feeding (expressed as δ13C) and contaminant loads. (4) PBDEs were not detected in significant amounts at either site. The results of this study indicate that the outflow from one of Europe’s largest river systems is associated with significant historical contamination, reflected by the accumulation of contaminants in body tissues in a coastal benthivore predator. [less ▲]

Elasmobranchs can bioaccumulate considerable amounts of persistent organic pollutants (POPs) and utilize several reproductive strategies thereby influencing maternal transfer of contaminants. This study provides preliminary data on the POP transfer from pregnant females to offspring of three species (Atlantic stingrays, bonnethead, blacktip sharks) with different reproduction modes (aplacental, placental viviparity). Polychlorinated biphenyl (PCB) levels were generally higher than any other POPs. Stingrays and blacktip shark embryos contained the lowest POP concentrations while bonnetheads and the blacktip adult female had the highest concentrations. Results suggest that are more readily transferred from the mother to the embryo compared to what is transferred to ova in stingrays. Statistically significant differences in levels of selected POPs were found between embryos from the left and right uterus within the same litter as well as between female and male embryos within the same litter for bonnetheads, but not for the blacktip sharks. [less ▲]

Organohalogenated compounds are widespread in the marine environment and can be a serious threat to organisms in all levels of aquatic food webs, including elasmobranch species. Information about the ... [more ▼]

Organohalogenated compounds are widespread in the marine environment and can be a serious threat to organisms in all levels of aquatic food webs, including elasmobranch species. Information about the concentrations of POPs (persistent organic pollutants) and of MeO-PBDEs (methoxylated polybrominated diphenyl ethers) in elasmobranchs is scarce and potential toxic effects are poorly understood. The aims of the present study were therefore to investigate the occurrence of multiple POP classes (PCBs, PBDEs, DDXs, HCB, CHLs) and of MeO-PBDEs in various elasmobranch species from different trophic levels in estuarine and marine waters of the southeastern United States. Overall, levels and patterns of PCBs, PBDEs, DDXs, HCB, CHLs and of MeO-PBDEs varied according to the species, maturity stage, gender and habitat type. The lowest levels of POPs were found in Atlantic stingrays and the highest levels were found in bull sharks. As both species are respectively near the bottom and at top of the trophic web, with juvenile bull sharks frequently feeding on Atlantic stingrays, these findings further suggest a bioaccumulation and biomagnification process with trophic position. MeO-PBDEs were not detected in Atlantic stingrays, but were found in all shark species. HCB was not found in Atlantic stingrays, bonnetheads or lemon sharks, but was detected in the majority of bull sharks examined. Comparison with previous studies suggests that Atlantic stingrays may be experiencing toxic effects of PCBs and DDXs on their immune system. However, the effect of these compounds on the health of shark species remains unclear. [less ▲]

This paper investigates the dynamics of a real-life aerospace structure possessing a strongly nonlinear component with multiple mechanical stops. A full-scale finite element model is built for gaining ... [more ▼]

This paper investigates the dynamics of a real-life aerospace structure possessing a strongly nonlinear component with multiple mechanical stops. A full-scale finite element model is built for gaining additional insight into the nonlinear dynamics that was observed experimentally, but also for uncovering additional nonlinear phenomena, such as quasiperiodic regimes of motion. Forced/unforced, damped/undamped numerical simulations are carried out using advanced techniques and theoretical concepts such as numerical continuation and nonlinear normal modes. [less ▲]

in Risk Analysis : An Official Publication of the Society for Risk Analysis (2015), 35(1), 129-141

This paper draws on vulnerability analysis as it emerged as a complement to classical risk analysis, and it aims at exploring its ability of nurturing risk and vulnerability governance actions. An ... [more ▼]

This paper draws on vulnerability analysis as it emerged as a complement to classical risk analysis, and it aims at exploring its ability of nurturing risk and vulnerability governance actions. An analysis of the literature on vulnerability analysis allows us to formulate a threefold critique: first, vulnerability analysis has been treated separately in the natural and the technological hazards fields. This separation prevents vulnerability to unleash the full range of its potential, as it constraints appraisals into artificial categories and thus already closes down the outcomes of the analysis. Second, vulnerability analysis focused on assessment tools that are mainly quantitative, whereas qualitative appraisal is a key to assessing vulnerability in a comprehensive way and to informing policy-making. Third, a systematic literature review of case studies reporting on participatory approaches to vulnerability analysis allows us to argue that participation has been important to address the above, but it remains too closed down in its approach and would benefit from embracing a more open, encompassing perspective. Therefore, we suggest rethinking vulnerability analysis as one part of a dynamic process between opening-up and closing-down strategies, in order to support a vulnerability governance framework. [less ▲]

T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T-PLL cases identified in the registry in French Society for stem cell transplantation (SFGM-TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow-up for surviving patients of 33 (range, 6–103) months, 10 patients are still alive in continuous CR. Overall survival and progression-free survival estimates at 3 yr were 36% (95% CI: 17–54%) and 26% (95% CI: 14–45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2–24) months. Overall cumulative incidence of transplant-related mortality was 31% at 3 yr. These results suggest that HSCT may allow long-term survival in patients with T-PLL following induction treatment; however, it is associated with a significant rate of toxicity. [less ▲]

Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an ... [more ▼]

Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells isolated from patients but little or no effect in PBMCs. Among the main phenolic compounds present in this bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside showed the highest apoptotic effect on B CLL cells, suggesting that anthocyanins play a main role in the cytotoxic activity. Antho 50-induced apoptosis is associated with activation of caspase 3 and down-regulation of the anti-apoptotic protein UHRF1. Antho 50 induced also rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2 resulting in reduced cell viability. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced reduced cell viability, induction of apoptosis, up-regulation of caspase 3, down-regulation of UHRF1 and Bcl-2, and dephosphorylation of Bad. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of Bad/Bcl-2 pathway. This activity is due, at least in part, to a composition rich on glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells. [less ▲]